Morphometry of Cortical Neurons in Acute Clozapine and Ethanol Poisoning

Баширова, А. Р.; Сундуков, Д. В.; Babkina, Anastasiya S.; Голубев, М. А.; Телипов, И Н

doi:10.15360/1813-9779-2020-6-19-30

Cited by 3 publications

(3 citation statements)

References 29 publications

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“…Изучение морфологических и функциональных нарушений, возникающих в центральной нервной системе при критических состояниях, является одной из наиболее значимых проблем анестезиологии и реаниматологии [37]. В настоящее время подробно изучены патологические изменения в коре головного мозга при отравлении этиловым спиртом, большинство из которых связаны с нарушениями гемодинамики.…”

Section: Discussionunclassified

Damage to neurons of the cerebral cortex in acute poisoning with baclofen and its combination with ethanol

Romanova

Голубев

Churiliv

et al. 2022

Russian Journal of Forensic Medicine

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The aim of the study was to identify and quantify cerebral cortex neuron damage in baclofen and baclofen ethanol poisoning. Material and methods.A histological study of 25 rat cerebral cortex was performed. The animals were divided into 5 groups. The controls received neither baclofen nor ethanol. Groups 1 and 3 received baclofen (85 mg/kg), groups 2 and 4 received baclofen (85 mg/kg) and ethanol (7 ml/kg). Group 1 and 3 animals were euthanized 4 hours, group 2 and 4 animals -24 hours after the drug administration. Histological sections were stained with hematoxylin and eosin and by Nissl method. We examined the sections by light microscopy (magnification 400x) and calculated the number of damaged neurons. Statistical processing was performed by nonparametric Mann-Whitney method. The share of neurons with reversible and irreversible changes in the controls was 13% and 9%. 4 hours after baclofen administration the share of neurons with reversible changes and irreversible changes was 22% and 21%. 4 hours after baclofen and ethanol administration we observed an increase in the share of reversible (24%) and irreversible (29%) changes of neurons. 24 hours after baclofen administration the share of reversible and irreversible changes was 25% and 37%. Baclofen and ethanol administration caused an increase in the share of neurons with reversible (27%) and irreversible (41%) changes. The difference s between group 3 (4 hours) and controls was significant; in group 4 (24 hours) the difference was significant in comparison to controls and to group 3 (4 hours). Understanding the processes occurring in the brain during baclofen and baclofen ethanol administration will allow to provide medical care to this category of patients more effectively. The identified signs of brain neuron damage, along with the results of forensic chemical analysis, can be used to establish the immediate cause of death.

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Section: Discussionunclassified

Damage to neurons of the cerebral cortex in acute poisoning with baclofen and its combination with ethanol

Romanova

Голубев

Churiliv

et al. 2022

Russian Journal of Forensic Medicine

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“…Morphological brain studies of the victims who died within 24 hours after poisoning with clozapine combined with alcohol revealed an acute brain neuronal damage, both non-specific reversible and irreversible, as well as blood circulation disorders including microcirculatory congestion, and perivascular and pericellular edema [10]. Experiments in rats demonstrated brain neuronal damage four hours after administration of a sublethal clozapine dose [11].…”

Section: Introductionmentioning

confidence: 99%

Global DNA Methylation Of Brain Neurons In Acute Poisoning With Clozapine And Its Combination With Alcohol: An Experimental Study

et al. 2021

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Background — Acute poisoning with atypical neuroleptic clozapine is characterized by rapid progression, high risk of death and severe neurological manifestations. Neurotoxic effects of this pharmaceutical drug have also been reported at therapeutic doses. The pathogenesis of brain damage in acute clozapine poisoning is not fully understood. Changes in DNA methylation level may play an important role in the mechanisms of drug neurotoxicity. The available data on the effect of clozapine on brain cell DNA provide a rationale for studying the epigenetic aspects of the pathogenesis of acute poisoning with this neuroleptic agent. The objective of our study was to evaluate the global DNA methylation level in rat brain neurons in acute poisoning with clozapine and its combination with ethanol. Material and methods — Clozapine – 150 mg/kg in 2.0 ml of normal saline solution, or clozapine – 150 mg/kg in 2.0 ml of 40% ethanol were administered via a gastric tube to adult male Wistar rats (n=21) under anesthesia with sevoflurane. In the control group, saline was administered via a gastric tube. Animals were euthanized four hours after drug administration. Autopsy was performed with the collection of brain samples for histochemical examination and determination of the DNA methylation level using the fluorometric method. To detect DNA in sections of paraffin-embedded tissue, we used the Feulgen staining. The TUNEL method was employed to detect DNA fragmentation. Results — An increase in the level of global DNA methylation in brain neurons was found in the clozapine and clozapine+ethanol groups. The average level of methylated DNA in the clozapine+ethanol group was higher than in the control group or clozapine group (2.56±0.31 vs. 1.35±0.1, p=0.007 and 1.70±0.33, p=0.044, respectively). An increase in the mean optical density of the cortical neuron nuclei was observed in the clozapine+ethanol group compared with the control group and clozapine group. DNA fragmentation was not detected in any experimental group. Conclusion — Acute poisoning with clozapine in combination with alcohol caused an increase in the global DNA methylation level in brain neurons, which may have played a significant role in the pathogenesis of acute clozapine poisoning and could be an important factor in the neurotoxicity of this medication.

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“…Cytotoxic cerebral edema occurs in poisoning or hypoxia as a result of cellular metabolic disorders and sodium and water retention in cells [1][2][3][4]. In most cases these processes are reversible.…”

Section: Introductionmentioning

confidence: 99%

Relation between the Severity of the Sensorimotor Cortical Edema with Cell Swelling and the Duration of Common Carotid Artery Occlusion in Rats (Morphometric Study)

Stepanov

Авдеев

Akulinin

et al. 2021

Obŝaâ reanimatologiâ

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The aim of the study. To examine the changes in structure and morphometry in sensorimotor cortical edema with cell swelling in mature white rats after common carotid artery occlusion of various durations.Material and methods. Acute ischemia was modeled on white adult Wistar rats by 20-, 30- and 40-min occlusion of the common carotid arteries (CCA). Histological (hematoxylin-eosin and Nissl staining), immunohistochemical (NSE, MAP-2, GFAP) and morphometric methods were used. Morphometry was assessed on hematoxylin and eosin-stained specimens using ImageJ 1.53 plug-ins (Find Maxima, Find Foci). Statistical hypothesis testing (nonparametric criteria) was performed using Statistica 8.0 software.Results. In the sensorimotor cortex (SMC) of white rats after 20, 30 and 40 minutes of CCA occlusion the signs of cytotoxic brain edema appeared, focal destructive and adaptive changes of neurons and astroglia evolved. The edema persisted throughout the observation period (7 days). The increase in the relative area, the number of cell swelling zones and their hydration (pixel brightness) was significant. On days 1 and 3 after CCA occlusion, some of the SMC astrocyte processes underwent destruction. Subpial and perivascular zones suffered to a greater extent. Mild and moderate (after unilateral 30-min CCA occlusion) to moderate and severe (after bilateral 40-min CCA occlusion) scattered structural and functional changes of the SMC with large areas of clearing in the «porous» neuropil, severe perivascular and perineuronal edema of the astrocyte processes developed. The latter was associated with a moderate reduction of the total neuronal density.Conclusion. After occlusion of CCA, signs of edema with cellular swelling appeared in the SMC amid dystrophic and necrotic pyramidal neurons and activated neuroglial cells. To a greater extent, the signs of brain swelling were evident three days after bilateral 40-min occlusion of CCA.

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Morphometry of Cortical Neurons in Acute Clozapine and Ethanol Poisoning

Cited by 3 publications

References 29 publications

Damage to neurons of the cerebral cortex in acute poisoning with baclofen and its combination with ethanol

Damage to neurons of the cerebral cortex in acute poisoning with baclofen and its combination with ethanol

Global DNA Methylation Of Brain Neurons In Acute Poisoning With Clozapine And Its Combination With Alcohol: An Experimental Study

Relation between the Severity of the Sensorimotor Cortical Edema with Cell Swelling and the Duration of Common Carotid Artery Occlusion in Rats (Morphometric Study)

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